BRCA2 carriers had an SIR of 4.45 (95% confidence interval [CI] 2.99-6.61) and absolute PCa risk of 27% (95% CI 17-41%) and 60% (95% CI 43-78%) by ages 75 and 85 yr, respectively.
Our findings provide a rationale for the future use of immune oncological approaches in BRCA2-mutated prostate cancer and may encourage efforts to target immunosuppressive T-cell populations to prime tumors for immunotherapy.
<i>Conclusions</i>: Our results provide a pre-clinical rationale for the use of 6-TG in the treatment of BRCA2-deficient castration-resistant prostate cancers, and of certain 6-TG analogues for treatment of BRCA2-proficient prostate cancers.
Molecular testing determined that his t-NEPC tumor (but not his original adenocarcinoma) harbored complete copy number loss of BRCA2, as well as copy number loss of another HR gene - ataxia telangiectasia, mutated (ATM).
Survival and cell-cycle alterations were performed after drug treatments in isogenic DT40, DLD1, and OVCAR cell lines with BRCA1, BRCA2, or PALB2 deficiencies and in organoids cultured from prostate cancer patient-derived xenografts with BRCA2 loss.
Association with PCa risk was statistically significant for variants in BRCA2 (P < 0.001, OR = 5.65, 95% CI = 3.55-9.32), HOXB13 (P < 0.001, OR = 4.73, 95% CI = 2.84-8.19), and ATM (P < 0.001, OR = 2.86, 95% CI = 1.63-5.15).
IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception.
We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations.
As breast and prostate cancer share genetic risk factors, including rare, high-risk mutations (eg, in BRCA2), we hypothesized that some of these heritable methylation marks might also be associated with the risk of prostate cancer.
Therefore, the use of BRCA2 mutation as a clinical prognostic factor could help stratify the high-risk patients and provide clinical strategies for more effective targeted treatments for patients with prostate cancer.